The introduction of laparoscopic surgery two decades ago revolutionized general surgery by minimizing abdominal wall incisions. Other new minimally invasive surgical techniques seek to further limit the trauma to the abdominal wall by reducing the number of or eliminating incisions on the abdominal wall. It is unclear whether these new techniques have any advantages over traditional laparoscopy. Validated, standardized comparison methods of one minimally invasive procedure with another are missing. For minimally invasive procedures, complication rates are low, and traditional, physician reported outcomes such as morbidity and survival are not useful. Biomarker investigations, such as serum cytokines, have been inconsistent. Comparisons with clinical outcomes are missing. Thus, there is a lack of valid tools to assess outcomes for benign disease in the minimally invasive surgery realm. In other fields, patient-reported outcome measures, such as pain and fatigue, have been demonstrated to be key vital signs in comparing treatment efficacy. Advances in standardization and psychometric integrity such as the NIH supported Patient-Reported Outcomes Measures Information System (PROMIS), have facilitated these comparisons. Patient-reported outcomes have outperformed physician-reported outcomes for predicting survival and toxicity from treatment in clinical trials. Additionally, patient-reported outcome changes appear to be correlated with biologic and physiologic system changes. We propose to apply patient-reported outcome measures for the efficient, consistent, and well-validated comparison of novel minimally invasive surgical procedures with standard of care procedures. A randomized blinded study of the new single-port and the standard four-port laparoscopic cholecystectomy (a procedure performed for more than 750,000 patients/year) will serve as the model to evaluate the comparative effectiveness of minimally invasive surgical approaches. The global health short form questionnaire, longitudinal analog self assessment and pain scales will serve as outcome measures. In addition, we will obtain data on perioperative biochemical and physiologic biomarkers such as serum levels of inflammatory cytokines and heart rate variability. This will serve as pilot data for future investigations into he relationship of biomarkers and patient reported outcomes in minimally invasive surgery for benign disease.